title: Myocardial Infarction and Its Association with the Use of Nonselective NSAIDs: A Nested Case-Control and Time-to-Event Analysis.
abstract: OBJECTIVE
  In April 2005, the US Food and Drug Administration issued a public health advisory warning to health care clinicians about the cardiovascular (CV) safety of nonsteroidal anti-inflammatory drugs (NSAIDs). Although the warning about cyclooxygenase-2 selective NSAIDs was anticipated, little data exists about the CV safety of nonselective NSAIDs. We analyzed data from a group of NSAID users to determine if specific nonselective agents were associated with an increased risk of myocardial infarctions (MIs) and sudden cardiac death (SCD).
  
  
  METHODS
  A nested case-control design was used to study NSAID users ages 18 to 84 years. Cases were defined by a hospital admission for MI or an out-of-hospital SCD. Study control subjects were matched for age, sex, current Kaiser Permanente membership, and geographic location (Northern or Southern California). Odds ratios (OR) were estimated using conditional logistic regression.
  
  
  RESULTS
  Our base population included 1,394,764 NSAID users. From this population we identified 8143 cases and 31,496 matched study control subjects. The median time to event was <100 days for all NSAIDs. Two nonselective NSAIDs were associated with increased odds of adverse CV outcomes: indomethacin (OR, 1.27; 95% confidence interval, 1.04-1.56) and naproxen (OR, 1.14; 95% confidence interval, 1.00-1.30).
  
  
  CONCLUSIONS
  Our results suggest that some nonselective NSAIDs are associated with an increased risk of MI and SCD. We found the increased risk to be small compared with the risk associated with rofecoxib. Cardiovascular events occurred early in therapy. Caution is warranted with some nonselective NSAIDs, especially those for which other studies have found evidence of risk.
authors.forename: T Craig
authors.initials: TC
authors.lastname: Cheetham
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
authors.forename: David
authors.initials: D
authors.lastname: Campen
authors.forename: Rita
authors.initials: R
authors.lastname: Hui
authors.forename: Michele
authors.initials: M
authors.lastname: Spence
authors.forename: Gerald
authors.initials: G
authors.lastname: Levy
authors.forename: Stanford
authors.initials: S
authors.lastname: Shoor